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Early differential diagnosis of active TB infection is essential in optimizing treatment and reducing TB mortality, but is hampered by a lack of accurate and accessible diagnostics. Previously, we reported on complement component C1q, measured in serum by ELISA, as a candidate biomarker for active tuberculosis. In this work we further examine the dynamics of C1q as a marker of progressive TB disease in non-human primates (NHP). We assessed systemic and pulmonary C1q levels after experimental infection using high or low single dose as well as repeated limiting dose <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>Mtb<\/jats:italic>) challenge of macaques. We show that increasing C1q levels, either peripherally or locally, correlate with progressive TB disease, assessed by PET-CT imaging or post-mortem evaluation. Upregulation of C1q did not precede detection of <jats:italic>Mtb<\/jats:italic> infection by a conventional interferon-gamma release assay, confirming its association with disease progression. Finally, pulmonary vaccination with Bacillus Calmette Gu\u00e9rin also increased local production of C1q, which might contribute to the generation of pulmonary protective immunity. Our data demonstrate that NHP modelling of TB can be utilized to study the role of C1q as a liquid biomarker in TB protection and disease, complementing findings in TB patients.<\/jats:p>","DOI":"10.1038\/s41598-020-63041-4","type":"journal-article","created":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T10:02:56Z","timestamp":1586858576000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Systemic and pulmonary C1q as biomarker of progressive disease in experimental non-human primate tuberculosis"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5395-505X","authenticated-orcid":false,"given":"Karin","family":"Dijkman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalie","family":"Lubbers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole V.","family":"Borggreven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom H. 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Tuberculosis: advances and challenges in development of new diagnostics and biomarkers. The Lancet. Infectious diseases 18, e199\u2013e210 (2018).","journal-title":"The Lancet. Infectious diseases"},{"issue":"Suppl 2","key":"63041_CR3","doi-asserted-by":"publisher","first-page":"S21","DOI":"10.1093\/infdis\/jiu803","volume":"211","author":"M Pai","year":"2015","unstructured":"Pai, M. & Schito, M. Tuberculosis diagnostics in 2015: landscape, priorities, needs, and prospects. The Journal of infectious diseases 211(Suppl 2), S21\u201328 (2015).","journal-title":"The Journal of infectious diseases"},{"key":"63041_CR4","doi-asserted-by":"publisher","first-page":"e1006687","DOI":"10.1371\/journal.ppat.1006687","volume":"13","author":"TJ Scriba","year":"2017","unstructured":"Scriba, T. J. et al. Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease. 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